S. cerevisiae as a model for studying mutations in the human gene OPA1 associated with dominant optic atrophy and for drug discovery

L’atrofia ottica dominante (ADOA) è una malattia mitocondriale caratterizzata da difetti visivi, che si manifestano durante l’infanzia, causati da progressiva degenerazione delle cellule gangliari della retina (RGC). ADOA è una malattia genetica associata, nella maggior parte dei casi, a mutazioni nel gene OPA1 che codifica per la GTPasi mitocondriale OPA1, appartenente alla famiglia delle dinamine, principalmente coinvolta nel processo di fusione mitocondriale e nel mantenimento del mtDNA. Finora sono state identificate più di 300 mutazioni patologiche nel gene OPA1. Circa il 50% di queste sono mutazioni missenso, localizzate nel dominio GTPasico, che si pensa agiscano come dominanti negative. Questa classe di mutazioni è associata ad una sindrome più grave nota come “ADOA-plus”. Nel lievito Saccharomyces cerevisiae MGM1 è l’ortologo del gene OPA1: nonostante i due geni abbiano domini funzionali identici le sequenze amminoacidiche sono scarsamente conservate. Questo costituisce una limitazione all’uso del lievito per lo studio e la validazione di mutazioni patologiche nel gene OPA1, infatti solo poche sostituzioni possono essere introdotte e studiate nelle corrispettive posizioni del gene di lievito. Per superare questo ostacolo è stato pertanto costruito un nuovo modello di S. cerevisiae, contenente il gene chimerico MGM1/OPA1, in grado di complementare i difetti OXPHOS del mutante mgm1Δ. Questo gene di fusione contiene una larga parte di sequenza corrispondente al gene OPA1, nella quale è stato inserito un set di nuove mutazioni trovate in pazienti affetti da ADOA e ADOA-plus. La patogenicità di queste mutazioni è stata validata sia caratterizzando i difetti fenotipici associati agli alleli mutati, sia la loro dominanza/recessività nel modello di lievito. A tutt’oggi non è stato identificato alcun trattamento farmacologico per la cura di ADOA e ADOA-plus. Per questa ragione abbiamo utilizzato il nostro modello di lievito per la ricerca di molecole che agiscono come soppressori chimici, ossia composti in grado di ripristinare i difetti fenotipici indotti da mutazioni nel gene OPA1. Attraverso uno screening fenotipico high throughput sono state testate due differenti librerie di composti chimici. Questo approccio, noto con il nome di drug discovery, ha permesso l’identificazione di 23 potenziali molecole attive.

Developments in contact lens measurement:a comparative study of industry standard geometric inspection and optical coherence tomography

Purpose: The aim of this study was to compare a developmental optical coherence tomography (OCT) based contact lens inspection instrument to a widely used geometric inspection instrument (Optimec JCF), to establish the capability of a market focused OCT system. Methods: Measurements of 27 soft spherical contact lenses were made using the Optimec JCF and a new OCT based instrument, the Optimec is830. Twelve of the lenses analysed were specially commissioned from a traditional hydrogel (Contamac GM Advance 49%) and 12 from a silicone hydrogel (Contamac Definitive 65), each set with a range of back optic zone radius (BOZR) and centre thickness (CT) values. Three commercial lenses were also measured; CooperVision MyDay (Stenfilcon A) in −10D, −3D and +6D powers. Two measurements of BOZR, CT and total diameter were made for each lens in temperature controlled saline on both instruments. Results: The results showed that the is830 and JCF measurements were comparable, but that the is830 had a better repeatability coefficient for BOZR (0.065 mm compared to 0.151 mm) and CT (0.008 mm compared to 0.027 mm). Both instruments had similar results for total diameter (0.041 mm compared to 0.044 mm). Conclusions: The OCT based instrument assessed in this study is able to match and improve on the JCF instrument for the measurement of total diameter, back optic zone radius and centre thickness for soft contact lenses in temperature controlled saline.

Variations of local heat transfer coefficient in piped flow of viscous liquids

Measurements were carried out to determine local coefficients of heat transfer in short lengths of horizontal pipe, and in the region of an discontinuity in pipe diameter. Laminar, transitional and turbulent flow regimes were investigated, and mixtures of propylene glycol and water were used in the experiments to give a range of viscous fluids. Theoretical and empirical analyses were implemented to find how the fundamental mechanism of forced convection was modified by the secondary effects of free convection, temperature dependent viscosity, and viscous dissipation. From experiments with the short tube it was possible to determine simple empirical relationships describing the axial distribution of the local 1usselt number and its dependence on the Reynolds and Prandtl numbers. Small corrections were made to account for the secondary effects mentioned above. Two different entrance configurations were investigated to demonstrate how conditions upstream could influence the heat transfer coefficients measured downstream In experiments with a sudden contraction in pipe diameter the distribution of local 1u3se1t number depended on the Prandtl number of the fluid in a complicated way. Graphical data is presented describing this dependence for a range of fluids indicating how the local Nusselt number varied with the diameter-ratio. Ratios up to 3.34:1 were considered. With a sudden divergence in pipe diameter, it was possible to derive the axial distribution of the local Nusse1t number for a range of Reynolds and Prandtl numbers in a similar way to the convergence experiments. Difficulty was encountered in explaining some of the measurements obtained at low Reynolds numbers, and flow visualization techniques wore used to determine the complex flow patterns which could lead to the anomalous results mentioned. Tests were carried out with divergences up to 1:3.34 to find the way in which the local Nusselt number varied with the diameter ratio, and a few experiments were carried out with very large ratios up .to 14.4. A limited amount of theoretical analysis of the 'divergence' system was carried out to substantiate certain explanations of the heat transfer mechanisms postulated.

Nonlinear loop mirror-based all-optical signal processing in fiber-optic communications

All-optical data processing is expected to play a major role in future optical communications. The fiber nonlinear optical loop mirror (NOLM) is a valuable tool in optical signal processing applications. This paper presents an overview of our recent advances in developing NOLM-based all-optical processing techniques for application in fiber-optic communications. The use of in-line NOLMs as a general technique for all-optical passive 2R (reamplification, reshaping) regeneration of return-to-zero (RZ) on-off keyed signals in both high-speed, ultralong-distance transmission systems and terrestrial photonic networks is reviewed. In this context, a theoretical model enabling the description of the stable propagation of carrier pulses with periodic all-optical self-regeneration in fiber systems with in-line deployment of nonlinear optical devices is presented. A novel, simple pulse processing scheme using nonlinear broadening in normal dispersion fiber and loop mirror intensity filtering is described, and its employment is demonstrated as an optical decision element at a RZ receiver as well as an in-line device to realize a transmission technique of periodic all-optical RZ-nonreturn-to-zero-like format conversion. The important issue of phase-preserving regeneration of phase-encoded signals is also addressed by presenting a new design of NOLM based on distributed Raman amplification in the loop fiber. © 2008 Elsevier Inc. All rights reserved.

Spatially-multiplexed fibre-optic Bragg grating strain and temperature sensor system based on interferometric wavelength-shift detection

A prototype fibre-optic system using interferometric wavelength-shift detection, capable of multiplexing up to 32 fibre-optic Bragg grating strain and temperature sensors with identical characteristics, has been demonstrated. This system is based on a spatially multiplexed scheme for use with fibre-based low-coherence interferometric sensors, reported previously. Four fibre-optic Bragg grating channels using the same fibre grating have been demonstrated for measuring quasi-static strain and temperature.

All optical networking beyond 10 Gbits/s OTDM networks based on electro-optic modulators and fibre ring lasers

This thesis examines options for high capacity all optical networks. Specifically optical time division multiplexed (OTDM) networks based on electro-optic modulators are investigated experimentally, whilst comparisons with alternative approaches are carried out. It is intended that the thesis will form the basis of comparison between optical time division multiplexed networks and the more mature approach of wavelength division multiplexed networks. Following an introduction to optical networking concepts, the required component technologies are discussed. In particular various optical pulse sources are described with the demanding restrictions of optical multiplexing in mind. This is followed by a discussion of the construction of multiplexers and demultiplexers, including favoured techniques for high speed clock recovery. Theoretical treatments of the performance of Mach Zehnder and electroabsorption modulators support the design criteria that are established for the construction of simple optical time division multiplexed systems. Having established appropriate end terminals for an optical network, the thesis examines transmission issues associated with high speed RZ data signals. Propagation of RZ signals over both installed (standard fibre) and newly commissioned fibre routes are considered in turn. In the case of standard fibre systems, the use of dispersion compensation is summarised, and the application of mid span spectral inversion experimentally investigated. For green field sites, soliton like propagation of high speed data signals is demonstrated. In this case the particular restrictions of high speed soliton systems are discussed and experimentally investigated, namely the increasing impact of timing jitter and the downward pressure on repeater spacings due to the constraint of the average soliton model. These issues are each addressed through investigations of active soliton control for OTDM systems and through investigations of novel fibre types respectively. Finally the particularly remarkable networking potential of optical time division multiplexed systems is established, and infinite node cascadability using soliton control is demonstrated. A final comparison of the various technologies for optical multiplexing is presented in the conclusions, where the relative merits of the technologies for optical networking emerges as the key differentiator between technologies.

Interrogation of fibre optic sensors

The aim of the research work described in this thesis was to investigate the interrogation of fibre optic sensors using "off the shelf optical components and equipment developed mainly for the telecommunications industry. This provides a cost effective way of bringing fibre optic sensor systems to within the price range of their electro-mechanical counterparts. The research work focuses on the use of an arrayed waveguide grating, an acousto-optic tuneable filter and low-coherence interferometry to measure dynamic strain and displacement using fibre Bragg grating and interferometric sensors. Based on the intrinsic properties of arrayed waveguide gratings and acousto-optic tuneable filters used in conjunction with interferometry, fibre Bragg gratings and interferometric sensors a number of novel fibre optic sensor interrogation systems have been realised. Special single mode fibre, namely, high-birefringence fibre has been employed to implement a dual-beam interrogating interferometer. The first interrogation scheme is based on an optical channel monitor, which is an arrayed waveguide grating with integral photo-detectors providing a number of amplified electrical outputs. It is used to interrogate fibre Bragg grating and interferometric sensors. Using the properties of polarisation maintainability in high-birefringent fibre an interrogating interferometer was realised by winding a length of the fibre around a piezoelectric modulator generating a low-frequency carrier signal. The system was used to interrogate both fibre Bragg grating and interferometric sensors. Finally, the use of an acousto-optic tuneable filter is employed to interrogate fibre Bragg gratings. The device is used to generate a very high frequency carrier signal at the output of an optical interferometer.

Local heat transfer coefficient in a baffled shell and tube heat exchanger

Local shell side coefficient measurements in the end conpartments of a model shell and tube heat exchanger have been made using an electrochemical technique. Limited data are also reported far the second compartment. The end compartment average coefficients have been found to be smaller than reported data for a corresponding internal conpartment. The second compartment data. have been shown to lie between those for the end compartments and the reported internal compartment data. Experimental data are reported fcr two port types and two baffle orientations. with data for the case of an inlet compartment impingement baffle also being given . Port type is shown to have a small effect on compartment coefficients, these being largely unaffected. Likewise, the outlet compartment average coefficients are slightly snaller than those for the inlet compartment, with the distribution of individual tube coefficients being similar. Baffle orientation has been shown to have no effect on average coefficients, but the distribution of the data is substantially affected. The use of an impingement baffle in the inlet compartment lessens the efect of baffle orientation on distribution . Recommendations are made for future work.

Optic flow in human vision: MEG reveals a foveo-fugal bias in V1, specialization for spiral space in hMSTs, and global motion sensitivity in the IPS

Abstract We recorded MEG responses from 17 participants viewing random-dot patterns simulating global optic flow components (expansion, contraction, rotation, deformation, and translation) and a random motion control condition. Theta-band (3–7 Hz), MEG signal power was greater for expansion than the other optic flow components in a region concentrated along the calcarine sulcus, indicating an ecologically valid, foveo-fugal bias for unidirectional motion sensors in V1. When the responses to the optic flow components were combined, a decrease in MEG beta-band (17–23 Hz) power was found in regions extending beyond the calcarine sulcus to the posterior parietal lobe (inferior to IPS), indicating the importance of structured motion in this region. However, only one cortical area, within or near the V5/hMT+ complex, responded to all three spiral-space components (expansion, contraction, and rotation) and showed no selectivity for global translation or deformation: we term this area hMSTs. This is the first demonstration of an exclusive region for spiral space in the human brain and suggests a functional role better suited to preliminary analysis of ego-motion than surface pose, which would involve deformation. We also observed that the rotation condition activated the cerebellum, suggesting its involvement in visually mediated control of postural adjustment.

Nitrogen cycle of effluent-irrigated energy crop plantations:from wastewater treatment to thermo-chemical conversion processes

This paper reviews nitrogen (N) cycle of effluent-irrigated energy crop plantations, starting from wastewater treatment to thermo-chemical conversion processes. In wastewater, N compounds contribute to eutrophication and toxicity in water cycle. Removal of N via vegetative filters and specifically in short-rotation energy plantations, is a relatively new approach to managing nitrogenous effluents. Though combustion of energy crops is in principle carbon neutral, in practice, N content may contribute to NOx emissions with significant global warming potential. Intermediate pyrolysis produces advanced fuels while reducing such emissions. By operating at intermediate temperature (500°C), it retains most N in char as pyrrolic-N, pyridinic-N, quaternary-N and amines. In addition, biochar provides long-term sequestration of carbon in soils.

Computational modelling of the impact of particle size to the heat transfer coefficient between biomass particles and a fluidised bed

The fluid–particle interaction and the impact of different heat transfer conditions on pyrolysis of biomass inside a 150 g/h fluidised bed reactor are modelled. Two different size biomass particles (350 µm and 550 µm in diameter) are injected into the fluidised bed. The different biomass particle sizes result in different heat transfer conditions. This is due to the fact that the 350 µm diameter particle is smaller than the sand particles of the reactor (440 µm), while the 550 µm one is larger. The bed-to-particle heat transfer for both cases is calculated according to the literature. Conductive heat transfer is assumed for the larger biomass particle (550 µm) inside the bed, while biomass–sand contacts for the smaller biomass particle (350 µm) were considered unimportant. The Eulerian approach is used to model the bubbling behaviour of the sand, which is treated as a continuum. Biomass reaction kinetics is modelled according to the literature using a two-stage, semi-global model which takes into account secondary reactions. The particle motion inside the reactor is computed using drag laws, dependent on the local volume fraction of each phase. FLUENT 6.2 has been used as the modelling framework of the simulations with the whole pyrolysis model incorporated in the form of User Defined Function (UDF).

Genetics of optic atrophy: recent progress in understanding

This article considers the clinical symptoms associated with hereditary optic atrophy and reviews recent progress in our understanding the genetics of the disorder. The major genes linked to optic atrophy are identified and how defects in these genes could lead to the optic disc pathology is discussed.